Gel formulation for the prevention and treatment of gastrointestinal distress in horses and other species

ABSTRACT

A supplement for preventing and/or treating gastrointestinal distress, including ulcer conditions, in animals is disclosed. The supplement is in a gel form and comprises mastic gum and an emulsifying agent such as lecithin. The supplement may also comprise a vegetable oil, B vitamins, one or more prebiotics or probiotics, and one or more minerals as well as, pH buffers and flavoring. The amount of mastic gum is from about 1 to about 6 grams per 10 cubic centimeters of gel.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims priority to provisional application U.S. Ser.No. 62/574,442 filed Oct. 19, 2017 and to U.S. Ser. No. 16/078,909,filed Aug. 22, 2018 which was a national phase of InternationalApplication No. PCT/US2017/034055, filed May 23, 2017, which is acontinuation-in-part of U.S. Ser. No. 15/161,689, filed May 23, 2016,which granted as U.S. Pat. No. 9,694,042 on Jul. 4, 2017. Thisapplication is also related to U.S. Ser. No. 15/388,425, filed Dec. 22,2016, which granted as U.S. Pat. No. 9,993,498 on Jun. 12, 2018.

FIELD

Embodiments described herein are related to a nutritional supplement forthe treatment and/or prevention of gastrointestinal distress in horsesand other species of animals. The supplement may be in a gelformulation.

BACKGROUND AND SUMMARY OF THE INVENTION

The horse is a roaming animal with a gastro intestinal digestive systemdesigned for and accustomed to grazing up to 17 hours a day. Thus, thehorse's digestive system is specifically designed for the intake ofsmall quantities of feed over long periods of time. Horses and certainother animals did not evolve to develop the mechanism which turnsstomach acid on and off, like humans. Therefore, a horse's stomachtypically produces stomach acid 24 hours a day even when there is nofood present and such production can be up to 9 gallons of acidic fluidper day.

Stalled horses, with minimal access to pasture for grazing, are normallyfed 2-3 times per day which leads to the buildup of excess stomach acid,as the stomach is subjected to prolonged periods of time without feedpresent to neutralize the acid. As such, gastric ulcers are quite commonin domesticated/stalled horses and foals; their prevalence has beenestimated at from about 50% to about 90%, depending upon the populationsurveyed and type and level of athletic activity in which the horses areengaged.

Foals are often subject to stomach ulcers causing morbidity andmortality. Clinical signs of ulcers in foals include intermittent colic(after suckling or eating), frequent recumbency (this is common in foalssince this position seems to provide some relief from severe gastriculceration), intermittent nursing, diarrhea, poor appetite, grinding ofteeth and excessive salivation.

Adult horses with stomach ulcers may exhibit one or more clinical signsof ulcers including: poor appetite, attitude changes, decreasedperformance, reluctance to train or work, excessive recumbency, poorbody condition, rough hair coat, weight loss, low grade colic and/orloose feces. More serious cases will show abdominal pain (colic) and/orgrinding of the teeth. Others may walk away from food for a period oftime as if the horse experiences discomfort when the food first contactsthe stomach. Due to the range of common clinical signs of ulcers (andthe fact that some horses with ulcers show no outward signs), the onlyclinically proven way to diagnose and verify stomach ulcers in horses isthrough gastric endoscopy or gastroscopy. Unfortunately, this involvesplacing an endoscope into the horse's stomach to examine its innersurface. This is unpleasant for the horse and sometimes a complexprocedure for the veterinarian as it invariably requires anesthesia. Inaddition, this process can be very costly for the horse owner and alarge number of veterinarians do not have access to an endoscope; due tothe high cost basis for this type of equipment.

Unfortunately, currently available solutions for the prevention ortreatment of ulcers or other gastrointestinal distress require alicensed caregiver to prescribe an oral administration of expensivetreatments with a dosing syringe. In addition to being costly, manyhorses or other animals fight this type of treatment, which makesadministration difficult.

What is needed is a method and supplement for prevention and/ortreatment of gastrointestinal distress, including ulcer conditions inhorses and other animal species. It would be further advantageous if themethod and supplement employed generally available materials, which weresafe and effective. It would be further advantageous if the supplementcould be provided in a variety of forms and could be readily formulatedwith existing equipment. Advantageously, the present inventionaccomplishes one or more up to all of the aforementioned needs.

In one embodiment, the present invention relates to a nutritionalsupplement for the prevention or treatment of gastrointestinal distressin animals comprising mastic gum and an emulsifying agent such aslecithin. The supplement may alternatively be used to support a healthydigestive tract in a broad range of animals. In another embodiment, thepresent invention relates to a method of preventing gastrointestinaldistress in an animal comprising: dosing an animal orally at least oncedaily with a supplement. The supplement comprises: mastic gum and anemulsifying agent such as lecithin in a weight ratio of mastic gum toemulsifying agent such as lecithin of from about 1:10 to about 1:50based on the total weight of mastic gum and emulsifying agent such aslecithin. In another embodiment, the invention pertains to a method ofpreventing or treating ulcer conditions in a horse. The method comprisesproviding an effective amount of a supplement to address and/or treatgastrointestinal distress. The supplement comprises mastic gum, anemulsifying agent such as lecithin, and optionally one or more Bvitamins, and one or more biotics selected from prebiotics, probiotics,and combinations thereof.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a diagram of the typical equine stomach.

DETAILED DESCRIPTION

The present invention pertains generally to a nutritional supplement forthe prevention or treatment of gastrointestinal distress in animals. Italso pertains generally to a method of preventing gastrointestinaldistress in an animal and more specifically to a method of preventing ortreating ulcer conditions in a horse using a nutritional supplement asdescribed herein.

As used herein “gastrointestinal distress” generally refers togastrointestinal upset, ulcers, and other digestive conditions ordisorders such as diarrhea that are suffered by non-human animals suchas a horse, dog, sheep, alpaca, llama, camel, cat, donkey, and cow. In apreferred embodiment, the animal is a horse. The supplements and methoddescribed herein may be useful to prevent gastrointestinal distressand/or treat gastrointestinal distress in various animals includingpigs, primates, guinea pigs, ferrets, elephants, marine mammals,rabbits, rats, dolphins, tigers, cheetahs, lions zebras, zoo animals,livestock, and domestic animals. Generally, the amount of supplementand/or dosage is higher when the supplements and/or methods are employedto treat as opposed to prevent distress. In certain instances anddosages, the supplements and/or methods may simultaneously treat andprevent further gastrointestinal distress.

FIG. 1 shows the typical equine digestive tract focusing on the stomach.The equine digestive process can be conceptually divided into thefunctions carried out in the front of the gastrointestinal tract andthose carried out in the back of the GI tract. The functions carried outin the two areas can be very different. In the foregut, after food isgathered up, chewed, and swallowed, the stomach kicks into gear. Themain functions of the stomach are to add gastric acid to help with thebreakdown of food, to secrete the enzyme pepsinogen to begin proteindigestion, and to regulate the passage of food into the small intestine.The stomach can be thought of as a holding and mixing tank, similar to acement truck that is constantly churning and mixing ingredients.

While food breakdown may begin in the stomach, it continues in the smallintestine, where secretions help with the further digestion of protein,simple carbohydrates, and fat. The small intestine is also the main siteof nutrient absorption once the food is in small enough form. Aminoacids, glucose, vitamins, minerals, and fatty acids are taken into thebody as they move along the small intestine, so progress shouldn't betoo fast or too slow.

The processes that occur in the hindgut, and particularly in the cecumand colon, are less about breaking down food into smaller, absorbableparticles with the aid of enzymes and more about fermenting complexcarbohydrates (fiber) into useful end products with the assistance ofbeneficial organisms. In addition to generating fatty acids, whichsupply energy or calories, these helpful microorganisms also produceB-vitamins, Vitamin K, and some amino acids. The colon then serves notonly to absorb these nutrients but also a portion of the water thataccompanies food as it moves along the digestive tract.

Mastic Gum and Emulsifying Agent Such as Lecithin Employed

The nutritional supplement generally comprises a mixture of mastic gumand an emulsifying agent such as lecithin. The types and amounts ofmastic gum employed may vary. That is, the specific properties andamounts of the mastic gum that may be employed herein, of course mayvary depending upon a number of factors including, for example, thedesired results, the animal being treated, as well as the types andamounts of other ingredients employed and the desired form of thesupplement.

The mastic gum (a source of triterpenic compounds and phytosterols) maybe produced synthetically or, alternatively and more preferably, readilyobtained from common natural sources. Mastic gum is sometimes known alsoas Chios Mastiha. Mastic gum is a natural resin that typically comesfrom an evergreen small tree or large shrub, which may be cultivatedsuccessfully in, for example, the Mediterranean such as the island ofChios, in the Eastern Aegean Sea. This evergreen tree called Schinos,belongs to the family of Pistachia. (Botanical name: Pistachia Lentiscusvar. Chia). Mastic gum useful in the present invention is availablecommercially from sources such as Parchem or other chemical ornutritional supplement suppliers.

The emulsifying agent or agents employed may vary depending upon anumber of factors including, for example, the desired results, theanimal being treated as well as the types and amounts of otheringredients employed, and the desired form of the supplement. While notwishing to be bound to any theory it is believed that including asuitable amount of a emulsifying agent may assist in delivery of themastic gum to the stomach lining by virtue of being at least partiallysoluble in one or more fats present in the stomach and water. Theemulsifying agent may aid in protecting gastric tissue from ulcer injuryin, for example, horses and other animals. First, the mastic/emulsifyingagent may facilitate forming a barrier between stomach contents andepithelial cells, and second, one or both ingredients may facilitatecell membrane turnover and wound resealing. The emulsifying agent mayalso assist in partially protecting the mastic gum from being destroyedby excess stomach acid and/or in maintaining an appropriate texture ofthe mastic gum depending upon the form of the supplement.

Useful emulsifying agents may include any agent that is compatible withmastic gum and relatively non-toxic to normal cells. Such emulsifyingagents are often found in food products such as dairy products like icecream, butter, and margarine, salad dressings, and mayonnaise. Suchemulsifying agents are also described in TITLE 21—FOOD AND DRUGS,CHAPTER I—FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMANSERVICES, SUBCHAPTER E—ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS, PART582 Subpart E—Emulsifying Agents, SUBSTANCES GENERALLY RECOGNIZED ASSAFE and currently include Diacetyl tartaric acid esters of mono- anddiglycerides of edible fats or oils, or edible fat-forming fatty acids;Mono- and diglycerides of edible fats or oils, or edible fat-formingacids; Monosodium phosphate derivatives of mono- and diglycerides ofedible fats or oils, or edible fat-forming fatty acids; Monosodiumphosphate derivatives of mono- and diglycerides of edible fats or oils,or edible fat-forming fatty acids; Propylene glycol; and mixturesthereof. Useful emulsifying agents may also include, for example,lecithin, calcium sterol, soy lecithin, monoglycerides, alkali stearatessuch as magnesium stearate and potassium stearate, sucrose ester,ethoxylated sorbitan esters (trade name: TWEEN such as TWEEN20 andTWEEN80), xanthum gum, guar gum, peptin, methyl cellulose, glycol esterssuch as propylene glycol ester, sorbitan esters such as sorbitanmonostearate (trade name SPANS), glyceryl monostearate, tragacanth,sodium lauryl sulfate, sodium dioctyl sulfosuccinate, and mixturesthereof.

Generally, lecithin is a naturally occurring fatty substance orphospholipid, which could potentially be produced synthetically ifdesired. Lecithin may come from many sources, including both plant andanimal tissues. Soybeans are the most common source of lecithin (soylecithin), but other potential sources of lecithin include: eggs, animaltissues, milk, fish eggs, rapeseed, cotton seed and sunflower. Oneparticularly preferable emulsifying agent is lecithin which is believedto act synergistically with mastic gum at certain proportions withrespect to its use in equine animals. While not wishing to be bound toany particular theory one potential reason that soy lecithin may beparticularly effective is that soy lecithin comprisesphosphatidylethanolamines which are also found in the lipid bilayer ofmost cells.

A chemical formula for a lecithin is C₈H₁₇O₅NRR′ wherein R and R′ arethe same or different fatty acid groups. Pure lecithin is generally aphosphatidyl choline. That is, lecithins are mixtures of diglycerides offatty acids linked to the choline ester of phosphoric acid. Thus,lecithins are often classed as phosphoglycerides or phosphatides(phospholipids). Commercially available lecithin is often a mixture ofacetone insoluble phosphatides. For example, LECITHIN FCC, availablefrom, for example, Spectrum Chemical, is a substance that is of a fattynature and occurs naturally in animals and plant tissues. It is abrownish yellow color and contains a range of substances such astriglycerides, glycerol, phosphoric acid and so on. Other potentialsources of lecithin useful in the present invention include, forexample, Cargill.

The specific emulsifying agent such as lecithin and amounts employed inthe supplements and method of treatment/prevention also vary dependingupon a number of factors. Such factors include, for example, the desiredresults, the animal being treated as well as the types and amounts ofother ingredients employed and the form of the supplement. So long asthe emulsifying agent such as lecithin is capable of being mixed withthe mastic gum, it may be in any form. Preferably, the emulsifying agentsuch as lecithin with mastic gum employed may be in a form such asgranules, powders, or even liquid such that it may be substantiallyhomogeneously mixed with the mastic gum. Suitable forms for thesubstantially homogeneous mixture include, for example, top dressings asdescribed herein. Moreover, such mixtures include, for example, oralgels and “extruded treats”. Oral gels may include, for example, a gelcomprising the ingredients and amounts described herein or alternativelyfrom at least about 1, 1.5, 2, 2.5, or 3 or more grams per dose with orwithout a time release component. Such gels may typically comprise lessthan about 6, 5, 4.5, 4, 3.5, or 3 or less grams per dose with orwithout a time release component.

“Extruded Treat” as used herein means a formulation in the form of, forexample, a snack or other supplement to be provided at, for example, anon-routine feeding. Such extruded treats can comprise an appropriateamount of ingredients described herein or alternatively from at leastabout 0.5, 1, 1.5, 2, 2.5, or 3 or more grams per dose with or without atime release component. Such extruded treats may typically comprise lessthan about 6, 5, 4.5, 4, 3.5, or 3 or less grams per dose with orwithout a time release component. Often such extruded treats are madevia extrusion and are in the form of a solid such as a chewable biscuitsimilar to MILK BONE dog treats.

Weight Ratios and Amounts of Mastic Gum and Emulsifying Agent Such asLecithin Employed

As described previously, the amounts of mastic gum and emulsifying agentsuch as lecithin employed vary depending upon a number of factorsincluding, for example, the degree or severity, if any, ofgastrointestinal distress, desired results, the animal being treated aswell as the types and amounts of other ingredients employed and the formof the supplement. Other factors may include, for example, the activitylevel and/or diet of the animal.

Generally, the weight ratio of mastic gum to emulsifying agent such aslecithin is determined such that the weight ratio is effective toprevent and/or treat gastrointestinal distress in an animal by providingthe animal with about one to two or three or even four supplements perday. In such cases, the weight ratio of mastic gum to emulsifying agentsuch as lecithin is a range from about 1:2500 to about 1:1.25, or fromabout 1:1000 to about 1:300, or from about 1:500 to about 1:100, or fromabout 1:10 to about 1:50 based on the total weight of mastic gum andemulsifying agent such as lecithin. In other embodiments, the ratio ofmastic gum to emulsifying agent such as lecithin is a range from about1:1 to about 1:100, or from about 1:10 to about 1:50, or from about 1:20to about 1:40, or is a range from about 1:15 to about 1:35, or fromabout 0.5:40. to about 1.5:20.

Some embodiments may comprise the step of identifying an animal withulcer conditions for treatment. A preferred embodiment also comprisesthe step of dosing an animal with the supplement for at least thirtydays.

Supplement Form and Process of Making

The nutritionally supplement comprising lecithin, mastic gum and/orother ingredients is typically administered or provided orally to theanimal in any convenient manner. The supplement may be formulated as apowder, paste, granule, liquid, gel, capsule, tablet or pellets. Variousadditives may be added to the supplement in order to achieve the desiredphysical form. In one embodiment, the supplement may be administered orprovided as a top dressing on top of food at one or more regular dailyfeeding times. A top dress is typically a formulation that is asupplement form which encourages the animal to ingest the supplementvoluntarily. That is, if the supplement is not in the form of a “topdressing”, then the animal may move the supplement to the side, spit outthe supplement, or refuse the feeding altogether.

The specific process of making the supplement, of course, will varydepending upon the final form desired, the specific ingredients andtheir form, amounts employed, and other factors. Generally, the processtypically involves mixing the desired emulsifying agent such as lecithinand mastic gum at ambient conditions to form a substantially homogenousmixture. If other ingredients are desired in the supplement, then inmost cases the ingredients may be mixed prior to, simultaneously or evenafter the emulsifying agent such as lecithin and mastic gum are mixed.In some cases, it may be desirable to add the desired amounts ofemulsifying agent such as lecithin and mastic gum to an alreadycommercially available supplement lacking sufficient amounts of lecithinand mastic gum. Once the desired ingredients are mixed, they may be putin the desired form, e.g., powder, paste, granule, liquid, gel, orpellets using techniques known to those skilled in the art.

Other Ingredients

Other ingredients may be added to the supplement so long as theingredients do not substantially interfere with the desired effects ofthe supplement comprising mastic gum and emulsifying agent such aslecithin. In certain embodiments, the supplement may additionallycomprise beneficial amounts of biotics such as probiotics and/orprebiotics, vitamins, minerals, and/or other nutritional supplements.

Probiotics are live “good” microorganisms, such as bacteria and yeast.Probiotics that may be useful in the supplement, particularly for equinesupplements, include Enterococcus faecium, Lactobacillus acidophilus,Lactobacillus caseii and Lactobacillus plantarum. Additional potentialprobiotics may include:

Lactobacillus species including, but not limited to, L. rhamnosus, L.salivarius, L. paracasei, L. gasseri, L. reuteri, L. bulgaricus, L.brevis, L. brevis, L fermentum, and L. reuteri.

Bifidobacterium species including, but not limited to, B. bifidum, B.longum, B. infantis, B. breve, and B. lactis.

Bacillus species including, but not limited to, B. coagulans and B.subtillius.

Streptoccocus species including, but not limited to, S. salivarius, S.thermophilus, S. cremoris, S. faecium and S. infantis.

Other useful species may include, but are not limited to, Saccharomycesboulardii, Aspergillus oryzae, Saccharomyces cerevisiae, and Aspergillusniger.

The amount of probiotic to include in the supplement varies dependingupon, among other items, the type of probiotic, other ingredients, anddesired results. Typically, an amount of probiotic is measured in colonyforming units (CFU's) per dose. In many cases, from millions to evenbillions of CFUs of probiotic may be included in a given supplement.Typically, the amount of probiotic may be at least 500 million,preferably at least 1 billion, more preferably at least 2 billion,preferably at least 3 billion up to as much as 10 billion CFUs per doseof supplement. Certain embodiment may comprise at least 10 to 15 billionCFUS per dose of supplement.

Disclosed embodiments may comprise at least 500 million, preferably atleast 1 billion, more preferably at least 2 billion, preferably at least3 billion up to as much as 10 billion CFUs of each species ofLactobacillus acidophilus, Lactobacillus plantarum, Lactobacillus casei,and/or Enterococcus faecium per dose of supplement.

In contrast to probiotics, prebiotics are the foods that feed theprobiotics. Examples of prebiotic that may be included, particularly inequine supplements, include fructooligosaccharides (FOS),xylooligosaccrarides (XOS), polydextrose, pectin and psyllium.Additional potential prebiotics include the following:

Larch arabinogalactin (LAG), resistant starch, beta-glucans,trans-galactooligosaccharide, inulin, oligofructose, gum arabic, chicoryroot, Jerusalem artichoke, dandelion greens, garlic, leek, onion,asparagus, wheat bran, wheat flour, and banana.

Prebiotics may include short-chain prebiotic with 2-8 links persaccharide molecule or longer-chain prebiotics with 9-64 links persaccharide molecule. Prebiotics may comprise any of the above incombination as in Oligofructose-Enriched Inulin (OEI).

Prebiotic food ingredients are generally not digested by horses or otheranimals. Instead, prebiotics are digested by desirable microorganismsand probiotics in the digestive system to increase or enhance thenumbers and/or activity of the desirable microorganisms and/orprobiotics. Thus, including both probiotics and prebiotics in thesupplement may assist in further treating or preventing GI-relatedconcerns, such as diarrhea, by facilitating the growth of the goodmicrobes and/or minimizing the invasion and growth of disease-causingbacteria. Probiotics and/or prebiotics may be particularly preferable insupplements employed in animals such as horses that are on antibioticsor experiencing stress, transport, abrupt dietary changes, and/orClostridium or Salmonella infections. Any of these may potentially alterthe normal microbe population in, for example, a horse's largeintestine.

If prebiotics are to be employed in the supplement, then the amount mayvary widely depending upon, among other items, the type of prebiotic,other ingredients, and desired results. Typically, an amount ofprebiotic is at least about 0.01, or at least about 0.1, or at leastabout 0.4 up to about 1, or up to about 2 grams per dose.

In addition to mastic gum, emulsifying agent such as lecithin,probiotics and prebiotics, a wide variety of vitamins, minerals, orother nutritional supplements may be included in the describednutritional supplement. Such other ingredients include, for example, Bvitamins such as, for example, Vitamin B1 (thiamine) A coenzyme in thecatabolism of sugars and amino acids; Vitamin B2 (riboflavin) Aprecursor of cofactors called FAD and FMN, which are needed forflavoprotein enzyme reactions, including activation of other vitamins;Vitamin B3 (niacin or nicotinic acid) A precursor of coenzymes calledNAD and NADP, which are needed in many metabolic processes; Vitamin B5(pantothenic acid) A precursor of coenzyme A and therefore needed tometabolize many molecules; Vitamin B6 (pyridoxine, pyridoxal,pyridoxamine) A coenzyme in many enzymatic reactions in metabolism;Vitamin B7 (biotin) A coenzyme for carboxylase enzymes, needed forsynthesis of fatty acids and in gluconeogenesis; Vitamin B8 (inositol);Vitamin B9 (folic acid) A precursor needed to make, repair, andmethylate DNA; a cofactor in various reactions; especially important inaiding rapid cell division and growth, such as in infancy and pregnancy;Vitamin B12 (various cobalamins; commonly cyanocobalamin ormethylcobalamin in vitamin supplements) A coenzyme involved in themetabolism of every cell of the human body, especially affecting DNAsynthesis and regulation, but also fatty acid metabolism and amino acidmetabolism.

For certain embodiments, the ratio of total B-vitamins to mastic gum isfrom about 1:0.1 to about 1:4, or from about 1:0.3 to about 1:2, or fromabout 1:0.6 to about 1:1. B-vitamins may refer to all known B-vitaminsincluding: thiamine, riboflavin, niacin, nicotinic acid, pantothenicacid, pyridoxine, pyridoxal, pyridoxamine, biotin, folic acid, folinicacid, cyanocobalamin, methylcobalamin or other cobalamins, choline,adenine, or carnitine, adenosine monophosphate (AMP), inositol,para-aminobenzoic acid, pteryl-hepta-glutamic acid, orotic acid,dimethylglycine, L-carnitine, carnitine, and myo-inositol.

Other useful ingredients for the supplement may include DL methionine,Vitamin E, zinc, selenium, distillers dried grains with or withoutsolubles, magnesium mica, corn distillers dried grains, wheat middlings,alfalfa meal, dehydrated alfalfa, rice mill by product, rye flour, beetpulp, dicalcium phosphate, flaxseed meal, oat flour, oat oil, magnesiumstearate, cellulose, silicon dioxide, gelatin, maltodextrin, silica,fructose, inulin, inouline, soy protein isolate, rice bran, soybeanflour, coconut meal, marine lipid concentrates, kelp, kaolin, and/orpectin.

If desired, formulation aids and/or flavoring aids may be employed inthe supplement at useful amounts. Such ingredients include, for example,silicon dioxide, maltodextrin, vanilla flavor, and the like. Flavoringaids are typically added in a useful amount which encourages the animalto ingest the supplement voluntarily. Such aids include, for example,maltodextrin, vanilla flavor, and flavors such as fruit, vegetable,apple, honey, molasses, karo syrup, banana, citrus, orange, beet pulp,herbs, fenugreek, cherry, rosemary, cumin, carrot, peppermint, oregano,various flavors of jams and jellies. Suitable flavoring may be availableat various suppliers including, for example, Agriflavors, Inc. Someembodiments may contain a pH buffer or alkalinizing agent. Alternativeembodiments may contain an additive for coating the interior of ananimal stomach. Still other embodiments may contain anti-fungaladditives. Of the aforementioned additives it may be convenient toselect from those recognized as safe in TITLE 21—FOOD AND DRUGS, CHAPTERI—FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES,SUBCHAPTER E—ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS, PART 582Subparts A-H (Oct. 19, 2017 21 CFR 582.1-7724 incorporated herein byreference).

Chart 1 below shows a potential embodiment as well as potential dosageranges for the disclosed supplement. Such a supplement would beparticularly preferable for horses at a dose of about once daily forpreventing gastrointestinal distress. If desired, the supplement couldbe administered in two or even three or more daily doses for treatmentpurposes depending upon the severity of the distress. In certaincircumstances administering a dose every other day, every third day, orweekly may be appropriate depending on the nature and severity of thedistress. Generally, each of the below ingredients with the exception ofmastic gum and emulsifying agent such as lecithin are optional and thusneed not be present at even the low level described in Chart 1 below.That said, it is often preferable to include at least the prebiotics andprobiotics with the mastic gum and emulsifying agent such as lecithin.

If desired the composition may be formulated as a time releaseformulation. That is, the composition may further comprise on or moreingredients that facilitate release of the mastic gum in a controlledrelease over time. The skilled artisan will appreciate the type andamount of such ingredients as being used in conventional time releaseformulations. Such ingredients include, for example, methyl cellulosessuch as hydroxy methyl cellulose, hydroxy ethyl cellulose, and the likein amounts necessary to delay the release of the mastic gum for desiredamounts of time.

If desired, an absorbent may be added to the formulation. Useful amountsof such absorbents may be useful to, for example, facilitate removal ofheavy metals & toxins, balance pH levels, or both. Suitable absorbentmay include micronized zeolites such as clinoptilolite. Often, suchabsorbents may attract positive minerals such as calcium, magnesium,potassium, sodium and iron. These common positive cations may then bedisplaced by heavy metals such as cadmium, mercury, nickel, and arsenicand removed safely from the body.

Chart 1:

CHART 1 Dose Amount Range Formulation Low High Mastic Gum 1.00 gm 0.02gm 4.00 gm DL Methionine 1.72 gm 0.05 gm 3.00 gm Inositol 368 mg 100 mg550 mg Niacin 135 mg 10 mg 250 mg Thiamine 42 mg 10 mg 150 mg Riboflavin38 mg 10 mg 75 mg Pyridoxine 20 mg 5 mg 30 mg Biotin 2 mg 0.2 mg 20 mgVitamin B12 184 mcg 50 mcg 500 mcg Vitamin E 123 mg 30 mg 250 mg Zinc 1%0.03% 2% Selenium 40 ppm 10 ppm 100 ppm FOS - Prebiotics 0.5 gm 0.01 gm2.0 gm emulsifying agent 28.7 gm 5.0 gm 200 gm (Soy Lecithin)(preferably up to 50 gm) Probiotics 3 billion CFU's 500 million CFU's 10billion CFU's Lactobacillus acidophilus, Lactobacillus plantarum,Lactobacillus casei, Enterococcus faecium Silicon Dioxide 1%  .05% 2%Maltodextrin 2.8%     1% 5%

First Example Study Using the Formulation in Chart 1 Above in QuarterHorses

Eight quarter horses, which were actively engaged in racing or racetraining, were examined. These horses were positively diagnosed withsignificant and differing levels of Equine Gastric Ulcer Syndrome(EGUS), gastric erosions or lesions in the stomach. The gastric ulcersor lesions were verified through endoscopies on all horses in theinitial phase of the study. Inclusion criteria were horses specificallyshowing significant gastric ulceration and between the ages of 2-6years. The significant gastric ulceration was confirmed by gastro scopeand clinical observation. All horses selected were quarter horses inheavy training, most were young horses in race training.

The horses were all stalled and no changes in management occurred in thestudy time frame to confuse or affect the results of the study (i.e.horses removed from training, turned out to pasture or diet changes).These horses were all fed free choice Bermuda hay with a 14% sweet feedor Strategy as a grain source three times per day at three pounds eachfeeding. Additional supplementation included powder form electrolytes.None of the horses received any drug therapy thirty (30) days prior tostart of the study or during the study.

Three horses were randomly selected to receive the supplement 3× per day(horse #5, #6 and #7). Five horses were randomly selected to receive thesupplement 2× per day (horse #1, #2, #3, #4 and #8). The supplementprovided was in a one (1) ounce dose as in Chart 1 above (reproducedbelow).

Supplement Given 3× Per Day or 2× Per Day

Mastic Gum 1.00 gm DL Methionine 1.72 gm Inositol 368 mg Niacin 135 mgThiamine 42 mg Riboflavin 38 mg Pyridoxine 20 mg Biotin 2 mg Vitamin B12184 mcg Vitamin E 123 mg Zinc 1% Selenium 40 ppm FOS - Prebiotics 0.5 gmSoy Lecithin 28.7 gm Probiotics 3 billion CFU's Lactobacillusacidophilus, Lactobacillus plantarum, Lactobacillus casei, Enterococcusfaecium Silicon Dioxide 1% Maltodextrin 2.8%  

After ten days of product supplementation, urine samples were collectedfrom each horse and sent to an outside independent laboratory fortesting. After a minimum of thirty (30) days, all horses were examinedand endoscopies performed to evaluate product results.

All horses in the study showed good acceptance of the product, no sideeffects were reported and all horses tested negative for NSAIDS(non-steroidal anti-inflammatory drugs), Fluphenazine, Fluoetine andReserpine. After thirty (30) days of supplementation, all horses, exceptone, showed significant improvement after the 2× or 3× dailysupplements. The one horse that did not show improvement (Horse #8) wasultimately removed from the study due to the severity of the initial andongoing ulcerations and need for comprehensive treatment. For theremaining seven horses, improvement was observed, positively verifiedand documented through endoscopies performed on all horses.

In less than 60 days on the product, Horse #7 had numerous Grade II andGrade III ulcers reduced to Grade I Ulcer and Hyperkeratosis. Horse #5was diagnosed with Grade I and Grade II ulcers on 70% of the stomachwall. In less than 60 days on the product, this condition improved toGrade I ulcers and diffuse hyperkeratosis. Horse #7 initially showednumerous Grade II and Grade III ulcers and in a time period of just30-60 days on the product, these ulcers were ultimately reduced to GradeI Ulcer and Hyperkeratosis. Horse #5 was initially diagnosed with GradeI and Grade II ulcers on 70% of the stomach wall. In only 30-60 days onthe product, this condition improved and ultimately reduced to Grade Iulcers and diffuse hyperkeratosis.

Table 1 below shows the detailed assessments of the individual horsesbased on the initial gastroscope (positively diagnosing the severeulceration) and the follow-up gastroscope documenting the results afterproduct supplementation for 30-60 days.

TABLE 1 HORSE DAY 1 DAY 30-60 #1 Blister formation Hyperkeratosis 4 yr.old QH Hyperkeratosis Grade I ulcers on greater curvature of thestallion Multiple Grade I ulcers stomach #2 HyperkeratosisHyperkeratosis has improved 6 yr old QH Grade II ulcers Grade II ulcersremain gelding #3 Hyperkeratosis Hyperkeratosis improved 2 yr. old QHgelding #4 Grade I ulcers Grade III ulceration present 2 yr. old QHgelding #5 Grade I and Grade II ulcers on 70% Grade I ulcers, small indameter 2 yr. old QH of stomach wall Diffuse Hyperkeratosis filly #6Grade II and Grade III ulcers on lesser Grade II and Grade III ulcers onmargo 3 yr. old QH curvature of the stomach plicatis gelding Greatercurvature conctration and margo Hyperkeratosis on greater curvature ofthe plicatis stomach #7 Grade II and Grade III ulcers on 1- Grade Iulcer 2 yr. old QH greater curvature of the stomach Hyperkeratosisgelding Multiple superficial erosions #8 Hyperkeratosis on lessercurvature Marked Hyperkeratosis 2 yr old QH Grade II ulcers on 50% ofgreater curvature Grade I and Grade II ulcers on gelding of the stomachmargo plicatis *horse #8 was ultimately removed from the study due tothe severity of initial and ongoing ulcerations. Placed under care forcomprehensive treatment.

The results of this study show the positive effects of utilizing thisproduct in horses with severe gastric ulcers or lesions.

Terms and Definitions Used in the Example Study Above

Ulceration/Lesion Grading Scale:

0 Normal Grade I Intact Mucosa with reddening or hyperkeratosis Grade IIMild ulceration - small single or multifocal lesions, mildhyperkeratosis Grade Ill Moderate ulceration - large single or extensivemultifocal lesions Grade IV Severe ulceration - extensive lesions withareas of deep ulceration

Hyperkeratosis—term often used in connection with lesions of the mucousmembranes.

Margo Plicatus—cuticular ridge that separates the squamous mucosa fromthe glandular mucosa, in the equine stomach.

Recumbency—lying back or lying down, resting or leaning againstsomething else.

Ulcer conditions should be understood to include various levels ofEquine Gastric Ulcer Syndrome, gastric erosions, lesions in the stomachor other area of the digestive system in horses and other species.

Second Example Study in Quarter Horses

A second example study is being carried out in a similar manner to thatof the first example above except that the horses were provided only onedaily dose of the formulation listed in chart 1 above instead of the twoor three daily doses in the first example study. Preliminary findingsare below.

HORSE DAY 1 DAY 7 DAY 22 DAY 30 #9 Small pin point ulcers Resolvinggastric Exaggereted Lesser under cardiac sphincter ulcers epithelium, nocurvature Grade I ulcers on Film stuck to wall - no ulcer, Startedgreater ulcers Hyperkeratosis hauling and believed to be due working tohigh, intesnsity, harder high stress rodeo event riding 8 hours per dayjust 4 days earlier HORSE DAY 1 DAY 23 DAY 30 #10 Loose epithelium Nosign of ulcers No gastritis or Hyperkeratosis ulcers HORSE DAY 1 DAY 7DAY 10 DAY 14 DAY 30 #11 No ulcer No ulcer Hyperkeratosis HyperkeratosisStarted Hyperkeratosis Hyperkeratosis and gastritis but improved haulingand nearly gone working harder HORSE DAY 1 DAY 7 DAY 28 #12 No ulcerCoating over No ulcers Hyperkeratosis Hyperkeratosis Very Mild No ulcersHyperkeratosis on greater curvature

In another potential embodiment, ingredients may be formed into a geland administered as at least about 3, at least about 5, or at leastabout 8, or at least about 9, or at least about 10, or at least about11, or at least about 12, or at least about 15, or up to about a 20 cc(cubic centimeter) dose. Preferably, the currently described embodimentis administered in about a 10 cc dose. Alternatively, ingredients may beformed into a powder, paste, granule, liquid, or pellets. With regard tothe currently described embodiment below, ingredients are preferablyformed into a gel.

The terms “gel”, “gel formulation”, and “oral gel” are usedinterchangeably herein and generally refer to a dispersion which has aflowable, paste-like consistency (like toothpaste in one embodiment)such that it will, for example, flow under pressure such as that exertedby a human hand. In this manner the gel can be packaged in a tube,syringe, or other container and dispensed to the horse or other animal.In some embodiments the gel may be packaged within the barrel of aneedleless oral syringe marked with various dosages and dispensed bypushing a plunger into the barrel forcing the gel into the animal'smouth. The size of the syringe may vary but typically may comprise fromabout 3 to about 20 cc, e.g., 10 cc, of gel.

For example, a 10 cc dose of the currently described embodimentcomprises from at least about 1, or at least about 1.5, or at leastabout 2, or at least about 2.5, or at least about 3 or more grams ofmastic gum per dose or may comprise less than about 6, or less thanabout 5, or less than about 4.5, or less than about 4, or less thanabout 3.5, or less than about 3 or less grams per dose. With regard tothis particular embodiment, a 10 cc dose preferably contains about 3grams of mastic gum.

The currently described embodiment may comprise the Probiotic bacteria:Lactobacillus acidophilus, Lactobacillus plantarum, Lactobacillus caseiand/or Enterococcus faecium at at least about 2 billion, or at leastabout 3 billion, or at least about 3.5 billion, or at least about 4billion or more CFUs per 10 cc dose and/or may comprise less than about6 billion, or less than about 5 billion, or less than about 4.5 billion,or less than about 4 billion or less CFUs per 10 cc dose. With regard tothis particular embodiment, a dose preferably comprises Probioticbacteria: Lactobacillus acidophilus, Lactobacillus plantarum,Lactobacillus casei and/or Enterococcus faecium at about 4 billion CFUsper 10 cc dose. The probiotic bacteria to be added to the mixture toform the gel may be in any convenient form, for example, as the driedfermentation product.

The currently described embodiment comprises at least about 0.4 grams,or at least about 0.5 grams, or at least about 0.8 grams, or at leastabout 1 gram, or at least about 2 grams or more soy lecithin per 10 ccdose and/or may comprise less than about 1.5 grams, or less than about1.2 grams, or less than about 1 gram, or less soy lecithin per 10 ccdose. The currently described embodiment preferably comprises about 1gram soy lecithin per 10 cc dose. As described above, emulsifying agents(surfactants) other than soy lecithin may be employed and such is thecase in the currently described embodiment. That is, the emulsifyingagent may be selected from the group consisting of diacetyl tartaricacid esters of mono- and diglycerides of edible fats or oils, or ediblefat-forming fatty acids; mono- and diglycerides of edible fats or oils,or edible fat-forming acids; monosodium phosphate derivatives of mono-and diglycerides of edible fats or oils, or edible fat-forming fattyacids; monosodium phosphate derivatives of mono- and diglycerides ofedible fats or oils, or edible fat-forming fatty acids; propyleneglycol; lecithin; calcium sterol; soy lecithin; alkali stearates;sucrose ester; ethoxylated sorbitan esters; xanthum gum; guar gum;peptin; methyl cellulose; glycol esters; sorbitan esters; glycerylmonostearate; tragacanth; sodium lauryl sulfate; sodium dioctylsulfosuccinate; and mixtures thereof. The amount of emulsifying agentmay vary depending upon the specific agent, the amount of mastic, andthe other ingredients present but often the weight ratio of mastic gumto emulsifying agent may be from about 1:1 to about 5:1 based on theweight of mastic gum and emulsifying agent in the gel formulation.

The currently described embodiment may comprise, and preferably doescomprise, the prebiotic FOS. The amounts employed may vary dependingupon the application but usually are at least about 0.1 gram, or atleast about 0.2 grams, or at least about 0.3 grams or more, up to about1 gram, or up to about 0.9 grams, or up to about 0.7 grams per 10 ccdose. In one embodiment the amount of prebiotic FOS is about 0.5 gramsper 10 cc dose.

The currently described embodiment may be carried on an oil which isnaturally high in tocopherols to help preserve the integrity of theactive ingredients, preferably in gel form. The currently describedembodiment is preferably carried on soy oil and is more preferablycarried on non-GMO expelled soy oil. Other oils may also be employeddepending upon the specific ingredients, specific amounts, and desiredresults. Suitable oils may include vegetable oil such as those selectedfrom the group consisting of soybean oil, corn oil, rapeseed oil, canolaoil, sunflower oil, safflower oil, peanut oil, brazil nut oil,cottonseed oil, coconut oil, olive oil, palm oil, rice bran oil, grapeseed oil, hazelnut oil, linseed oil, safflower oil, sesame oil, andmixtures thereof. The amount of oil employed may vary depending upon thespecific oil, the amount of mastic, and the other ingredients presentbut often the amount of oil is more than the amount of mastic gum on aweight basis of the gel formulation. Often, by adjusting the type oramount of oil one may achieve the desired flowability of the gel, e.g.,the more oil that is present, the more flowable the composition is. Asuitable weight ratio range of oil to mastic gum may be from about 1.5:1to about 1:1 in some embodiments.

The manner of making the gel is not particularly critical so long as thegel exhibits the desired flowable paste-like consistency, remainssuitably mixed, and functions in the desired manner. Suitable methodsmay vary depending upon the specific amounts and specific ingredients.However, in general the mastic gum, vegetable oil, emulsifying agent,and any other desired ingredients are mixed in a convenient manner atambient temperature and pressure for a time sufficient to disperse thesolid ingredients relatively uniformly within the vegetable oil and anyother liquid ingredients. The desired flowable paste-like consistencycan be achieved primarily via adjusting the amounts of variousingredients and the skilled artisan may adjust the viscosity orflowability using conventional techniques and ingredients. Typically,the ingredients stay in a relatively homogenous mixture within the gelformulation at ambient conditions.

The method of using the gel formulation is similar to the methodsdescribed above for the various formulations. The animal is dosed orallyat least once daily with the gel formulation supplement when and asneeded to prevent or treat gastrointestinal distress. For example, ahorse in need of prevention could be dosed once daily for at least one,or at least two, or at least three days before a competition, heavytraining, trailering, or other stress conditions. A horse in need oftreatment for gastrointestinal distress or ulcers may be treated morefrequently and perhaps longer, e.g., once, twice, or three times dailyfor a period of at least a week, or least two weeks, or at least threeweeks, or at least four weeks. Similarly, there may be some horses thatmay be in need of a daily treatment for indefinite period of time. Atypical dose for an average size horse of 1000 to 1200 pounds is about10 cc of the above-described formulations. Of course, the dose can beincreased or decreased based on the size and needs of the horse.

Preparation of Gel Example

Approximately four kilograms of soy oil is added to three kilograms ofmastic gum, 1 kilogram of soy lecithin, and 0.5 kilogramsFOS—Prebiotics. The ingredients are mixed and 0.4 kilograms of silicondioxide and 4 billion CFU probiotics in dried fermentation form areadded while continuing to mix. If desired, B vitamins, flavoring aids,or other ingredients are added and mixed until a relatively homogeneousgel is obtained. If it is desired that the gel be more flowable, thenadditional soy oil may be added until the desired consistency isreached. The gel may then be put in 10 cc oral syringes.

The terms, descriptions and examples used herein are set forth by way ofillustration only and are not meant as limitations. Those skilled in theart will recognize that many variations are possible within the spiritand scope of the invention as defined in the following claims, and theirequivalents, in which all terms are to be understood in their broadestpossible sense unless otherwise indicated.

What is claimed is:
 1. A gel formulation for preventing gastrointestinaldistress in an animal comprising: mastic gum; soy lecithin; and soy oil;wherein the amount of mastic gum is from about 2 to about 4 grams per 10cubic centimeters of gel formulation.
 2. The gel formulation of claim 1wherein the amount of soy lecithin is from about 0.4 to about 2 gramsper 10 cubic centimeters of gel formulation.
 3. The gel formulation ofclaim 1 further comprising a probiotic.
 4. The gel formulation of claim1 further comprising a prebiotic.
 5. The gel formulation of claim 1further comprising one or more probiotics wherein the total amount ofone or more probiotics is from about 2 billion to about 6 billion CFUsper 10 cubic centimeters of gel formulation.
 6. The gel formulation ofclaim 5 wherein the one or more probiotics are selected from the groupconsisting of Enterococcus faecium, Lactobacillus acidophilus,Lactobacillus caseii, Lactobacillus plantarum, and mixtures thereof. 7.The gel formulation of claim 1 further comprising a flavoring aid. 8.The gel formulation of claim 1 further comprising a formulation aid. 9.The gel formulation of claim 8 wherein the formulation aid comprisessilicon dioxide.
 10. The gel formulation of claim 1 further comprisingdextrose.
 11. The gel formulation of claim 1 wherein the amount of soyoil is more than the amount of mastic gum on a weight basis of the gelformulation.
 12. A gel formulation for preventing gastrointestinaldistress in an animal comprising: mastic gum; an emulsifying agent; anda vegetable oil; wherein the amount of mastic gum is from about 1 toabout 6 grams per 10 cubic centimeters of gel.
 13. The gel formulationof claim 12 wherein the weight ratio of mastic gum to emulsifying agentis from about 1:1 to about 5:1 based on the total weight of mastic gumand emulsifying agent in the gel formulation.
 14. The gel formulation ofclaim 12 wherein the emulsifying agent is selected from the groupconsisting of diacetyl tartaric acid esters of mono- and diglycerides ofedible fats or oils, or edible fat-forming fatty acids; mono- anddiglycerides of edible fats or oils, or edible fat-forming acids;monosodium phosphate derivatives of mono- and diglycerides of ediblefats or oils, or edible fat-forming fatty acids; monosodium phosphatederivatives of mono- and diglycerides of edible fats or oils, or ediblefat-forming fatty acids; propylene glycol; lecithin; calcium sterol; soylecithin; alkali stearates; sucrose ester; ethoxylated sorbitan esters;xanthum gum; guar gum; peptin; methyl cellulose; glycol esters; sorbitanesters; glyceryl monostearate; tragacanth; sodium lauryl sulfate; sodiumdioctyl sulfosuccinate; and mixtures thereof.
 15. The gel formulation ofclaim 12 wherein the amount of vegetable oil is more than the amount ofmastic gum on a weight basis of the gel formulation.
 16. The gelformulation of claim 12 wherein the vegetable oil is selected from thegroup consisting of soybean oil, corn oil, rapeseed oil, canola oil,sunflower oil, safflower oil, peanut oil, brazil nut oil, cottonseedoil, coconut oil, olive oil, palm oil, rice bran oil, grape seed oil,hazelnut oil, linseed oil, safflower oil, sesame oil, and mixturesthereof.
 17. The gel formulation of claim 12 further comprising aprebiotic, a probiotic, or a mixture thereof.
 18. The gel formulation ofclaim 12 further comprising a flavoring aid.
 19. The gel formulation ofclaim 12 further comprising a formulation aid.
 20. A gel formulation forpreventing gastrointestinal distress in an animal comprising: mastic gumin an amount of from about 2 to about 4 grams of mastic gum per 10 cubiccentimeters of gel formulation; soy lecithin in an amount of from about0.4 to about 2 grams per 10 cubic centimeters of gel formulation; soyoil wherein the amount of soy oil is more than the amount of mastic gumon a weight basis of the gel formulation; anhydrous dextrose; silicondioxide; one or more prebiotics; and one or more probiotics.